Autonomic blockade improves insulin sensitivity in obese subjects

Area of Science:

• Metabolic Physiology
• Cardiovascular Regulation

Background:

• Obesity is a significant risk factor for insulin resistance.
• Compensatory increases in insulin levels may activate the sympathetic nervous system.
• Previous research indicated sympathetic activity does not improve resting energy expenditure in obesity.

Purpose of the Study:

• To test the hypothesis that sympathetic activation contributes to insulin resistance in obese individuals.
• To investigate the effect of autonomic blockade on insulin sensitivity and glucose uptake.

Main Methods:

• A hyperinsulinemic euglycemic clamp protocol was used to measure insulin sensitivity.
• Obese subjects underwent two conditions in a crossover design: saline (intact day) and trimetaphan (autonomic blockade).
• Whole-body glucose uptake (MBW) was assessed as an index of maximal muscle glucose use.

Main Results:

• Insulin-resistant subjects exhibited higher muscle sympathetic nerve activity compared to insulin-sensitive subjects.
• Autonomic blockade significantly improved glucose use in insulin-resistant individuals.
• No significant effect on glucose use was observed in insulin-sensitive subjects during autonomic blockade.

Conclusions:

• Sympathetic activation plays a role in the development of insulin resistance in obesity.
• This suggests a potential feedback loop where increased insulin levels exacerbate sympathetic activation.
• Targeting sympathetic activity may offer a novel approach for managing insulin resistance in obesity.